Subcellular localization of a promoter and an inhibitor of apoptosis (Smac/DIABLO and XIAP) during brain ischemia/reperfusion

We explored the expression of Smac/DIABLO, a newly identified mitochondrial apoptogenic molecule, and X-linked inhibitor of apoptosis protein (XIAP) in the brain subjected to ischemia/reperfusion. Transient focal ischemia was produced for 1 hour in mice. We observed only a negligible amount of Smac/DIABLO in both mitochondria and cytosol in the normal state. The mitochondrial expression level of Smac/DIABLO increased after 2-11 h reperfusion. There was increased Smac/DIABLO expression in the cytosol after 5 h reperfusion, implying the translocation of Smac/DIABLO into the cytosol. The subcellular localization of XIAP became more extensive within the cells during reperfusion, as compared with the normal state. Our results imply that Smac/DIABLO and XIAP are implicated in the pathophysiological mechanisms of reperfusion injury.